Mechanism Research of Magnetic Nanoparticle Fe₃O₄ and 5-Bromotetrandrine On Reversal of Multidrug Resistance in K562/A02 Leukemic Cells.

The present study aimed to research the machenism of magnetic nanoparticles Fe₃O₄ (Fe₃O₄-MNPs) and 5-bromotetrandrine (BrTet) on multidrug resistance cell line K562/A02 solitarily or symphysially.

The proliferation of K562 and K562/A02 cells, and the cytotoxicity of PMBCs which were cultured with daunomycin (DNR) alone or in combination with Fe₃O₄-MNPs (0.1, V/V), BrTet (0.5μM) or both for 48 h, were evaluated by MTT assay. DNR accumulation of K562, K562/A02 cells and PMBCs were analyzed by fluorospectrophotometry after incubated with 2μM DNR in the absence or presence with Fe₃O₄-MNPs (0.1 V/V), BrTet (0.5μM) or both for 48 h. Real time–PCR analyses and western blotting were performed to examine the mRNA and proteins level, respectively.

The results showed that the combination of Fe₃O₄-MNPs and BrTet with effective concentration could exaggerate cytotoxicity against MDR cell line K562/A02 significantly. Flow cytometry assay showed that 0.5μM BrTet in combination with Fe₃O₄-MNPs (0.1, V/V) significantly enhanced the intracellular accumulation of DNR in K562/A02 cells and its potency was greater than that of BrTet or Fe₃O₄-MNPs alone at the same concentrations. While both Fe₃O₄-MNPs and BrTet in company with DNR did not increase the cytotoxicity to PMBCs. Both BrTet and Fe₃O₄-MNPs inhibited the overexpression of MRP1, MRP2, MRP4 and MRP5, and down regulated, mrps mRNA expression in K562/A02 cells to some extent.

We propose that Fe₃O₄-MNPs loaded with DNR and BrTet probably have synergetic effect on reversal in multidrug resistance. However, this combination shows less cytotoxicity to normal cells and reveals better target. The results may provide evidence for clinic application of them as reversal agents of drug resistance.

No relevant conflicts of interest to declare.